Effective Antimalarial Treatment Research Articles

Compliance, Safety, and Effectiveness of Fixed-Dose Artesunate-Amodiaquine for Presumptive Treatment of Non-Severe Malaria in the Context of Home Management of Malaria in Madagascar

Home management of malaria is recommended for prompt, effective antimalarial treatment in children less than five years of age. Compliance, safety, and effectiveness of the new fixed-dose artesunate-amodiaquine regimen used to treat suspected malaria were assessed in febrile children enrolled in a 24-month cohort study in two settings in Madagascar. Children with fever were asked to visit community health workers. Presumptive antimalarial treatment was given and further visits were scheduled for follow-up. The primary endpoint was the risk of clinical/parasitologic treatment failure. Secondary outcomes included fever/parasite clearance, change in hemoglobin levels, and frequency of adverse events. The global clinical cure rate was 98.4% by day 28 and 97.9% by day 42. Reported compliance was 83.4%. No severe adverse effects were observed. This study provides comprehensive data concerning the clinical cure rate obtained with artesunate-amodiaquine and evidence supporting the scaling up of home management of malaria.

Malaria in pregnancy.

Malaria is a complex parasitic disease affecting about 32 million pregnancies each year in sub-Saharan Africa. Pregnant women are especially susceptible to malarial infection and have the risk of developing severe disease and birth complications. The target of Millennium Development Goal 6 is to end malaria deaths by 2015. Maternal and perinatal morbidity and mortality due to malaria may be reduced by implementing preventive measures, early diagnosis of suspected cases, effective antimalarial therapy and treatment of complications.

The Impact of Retail-Sector Delivery of Artemether–Lumefantrine on Malaria Treatment of Children under Five in Kenya: A Cluster Randomized Controlled Trial

It has been proposed that artemisinin-based combination therapy (ACT) be subsidised in the private sector in order to improve affordability and access. This study in western Kenya aimed to evaluate the impact of providing subsidized artemether-lumefantrine (AL) through retail providers on the coverage of prompt, effective antimalarial treatment for febrile children aged 3-59 months. We used a cluster-randomized, controlled design with nine control and nine intervention sublocations, equally distributed across three districts in western Kenya. Cross-sectional household surveys were conducted before and after the delivery of the intervention. The intervention comprised provision of subsidized packs of paediatric ACT to retail outlets, training of retail outlet staff, and community awareness activities. The primary outcome was defined as the proportion of children aged 3-59 months reporting fever in the past 2 weeks who started treatment with AL on the same day or following day of fever onset. Data were collected using structured questionnaires and analyzed based on cluster-level summaries, comparing control to intervention arms, while adjusting for other covariates. Data were collected on 2,749 children in the target age group at baseline and 2,662 at follow-up. 29% of children experienced fever within 2 weeks before the interview. At follow-up, the percentage of children receiving AL on the day of fever or the following day had risen by 14.6% points in the control arm (from 5.3% [standard deviation (SD): 3.2%] to 19.9% [SD: 10.0%]) and 40.2% points in the intervention arm (from 4.7% [SD: 3.4%] to 44.9% [SD: 11.7%]). The percentage of children receiving AL was significantly greater in the intervention arm at follow-up, with a difference between the arms of 25.0% points (95% confidence interval [CI]: 14.1%, 35.9%; unadjusted p = 0.0002, adjusted p = 0.0001). No significant differences were observed between arms in the proportion of caregivers who sought treatment for their child's fever by source, or in the child's adherence to AL. Subsidizing ACT in the retail sector can significantly increase ACT coverage for reported fevers in rural areas. Further research is needed on the impact and cost-effectiveness of such subsidy programmes at a national scale. Current Controlled Trials ISRCTN59275137 and Kenya Pharmacy and Poisons Board Ethical Committee for Clinical Trials PPB/ECCT/08/07.

Expanding the Antimalarial Drug Arsenal—Now, But How?

The number of available and effective antimalarial drugs is quickly dwindling. This is mainly because a number of drug resistance-associated mutations in malaria parasite genes, such as crt, mdr1, dhfr/dhps, and others, have led to widespread resistance to all known classes of antimalarial compounds. Unfortunately, malaria parasites have started to exhibit some level of resistance in Southeast Asia even to the most recently introduced class of drugs, artemisinins. While there is much need, the antimalarial drug development pipeline remains woefully thin, with little chemical diversity, and there is currently no alternative to the precious artemisinins. It is difficult to predict where the next generation of antimalarial drugs will come from; however, there are six major approaches: (i) re-optimizing the use of existing antimalarials by either replacement/rotation or combination approach; (ii) repurposing drugs that are currently used to treat other infections or diseases; (iii) chemically modifying existing antimalarial compounds; (iv) exploring natural sources; (v) large-scale screening of diverse chemical libraries; and (vi) through parasite genome-based (“targeted”) discoveries. When any newly discovered effective antimalarial treatment is used by the populus, we must maintain constant vigilance for both parasite-specific and human-related factors that are likely to hamper its success. This article is neither comprehensive nor conclusive. Our purpose is to provide an overview of antimalarial drug resistance, associated parasite genetic factors (1. Introduction; 2. Emergence of artemisinin resistance in P. falciparum), and the antimalarial drug development pipeline (3. Overview of the global pipeline of antimalarial drugs), and highlight some examples of the aforementioned approaches to future antimalarial treatment. These approaches can be categorized into “short term” (4. Feasible options for now) and “long term” (5. Next generation of antimalarial treatment— Approaches and candidates). However, these two categories are interrelated, and the approaches in both should be implemented in parallel with focus on developing a successful, long-lasting antimalarial chemotherapy.

Drug dispensing practices during implementation of artemisinin‐based combination therapy at health facilities in rural Tanzania, 2002–2005

To assess the degree to which policy changes to artemisinin-based combination therapies (ACTs) as first-line treatment for uncomplicated malaria translate into effective ACT delivery. Prospective observational study of drug dispensing practices at baseline and during the 3 years following introduction of ACT with sulfadoxine-pyrimethamine (SP) plus artesunate (AS) in Rufiji District, compared with two neighbouring districts where SP monotherapy remained the first-line treatment, was carried out. Demographic and dispensing data were collected from all patients at the dispensing units of selected facilities for 1 month per quarter, documenting a total of 271, 953 patient encounters in the three districts. In Rufiji, the proportion of patients who received a clinical diagnosis of malaria increased from 47.6% to 57.0%. A majority (75.9%) of these received SP + AS during the intervention period. Of patients who received SP + AS, 94.6% received the correct dose of both. Among patients in Rufiji who received SP, 14.2% received SP monotherapy, and among patients who received AS, 0.3% received AS monotherapy. The uptake of SP + AS in Rufiji was rapid and sustained. Although some SP monotherapy occurred, AS monotherapy was rare, and most received the correct dose of both drugs. These results suggest that implementation of an artemisinin combination therapy, accompanied by training, job aids and assistance in stock management, can rapidly increase access to effective antimalarial treatment.

Prevalence of asymptomatic malaria parasitaemia

Objective To evaluate factors associated with prevalence of malaria parasitaemia at first antenatal care visit. Methods The study was conducted at the University of Calabar Teaching Hospital from 1st June, 2007 to 31st July, 2007. A structured questionnaire was administered to a total of 545 pregnant women that were recruited in this study after obtaining informed consent and two slides of thin and thick films were prepared for each participant. Results Five hundred and twenty (95.4%) out of the 545 participants suffered from malaria parasitaemia, the rest 4.6% of those who had no parasitaemia had experienced symptomatic malaria before and were treated in private hospitals prior to their recruitment into the study. All participants (100%) who did not have antimalarials had parasitaemia compared with 91.1% among those that had antimalarials. The proportion of moderate to severe parasitaemia was also significantly higher among the former. Besides, the difference in parasitaemia between primigravidae and multigravidae was statistically significant ( P=0.000) too. Among the methods used for vector control, only insecticide treated nets (ITNS) was associated with significant reduction in the level of parasitaemia ( RR =0.83). Conclusion Malaria parasitaemia at first booking is significantly higher in primigravidae and women who have no anti-malaria treatment. The use of safe and effective antimalarial treatment along with ITNs will significantly reduce the level of parasitaemia in pregnant women.

Responses of caregivers to children under the age of five with fever and living in areas where malaria is endemic: a systematic review of qualitative studies.

The aim of this systematic review of qualitative studies was to provide a concise description of caregivers' responses to fever in children under the age of five and identify important factors that influence those responses. The review considered English language qualitative studies published between 1997 and 2007 which examined responses of caregivers to fever in children under the age of five and living in malaria endemic countries. We searched the following electronic databases: Pub Med, Social Sciences Citation Index, Academic search premier, Biomedical central, Direct Open Access Journals, Helsinki, Plos one, Scielo, Astmh, Blackwell Synergy, Elsevier, Oxford journals and popline using the following keywords or terms: "malarial fever", "under five children", responses, "prompt treatment", parents, "parental response", "treatment response", fever, malarial, "children under five", caregivers, guardians, "guardian response", parents, factors, malaria, and endemic. This process was complemented by searching Google Scholar and following up expert referrals. In areas where malaria is endemic, most cases of fevers are managed outside the formal health sector either in the homes or community. Caregivers, (generally parents, most often the mothers) are pivotal and play a critical role in provision of medical care for children with fevers. Responses of caregivers to fever in children under the age of five years are multiple but can broadly be categorised into two groups depending on the how soon after fever onset caregivers seek treatment for their children: early treatment seekers and late treatment seekers. Within each group, the specific actions taken by caregivers are variable and dynamic and commonly do not lead to the child with fever illness getting prompt and effective antimalarial treatment. In addition, numerous social, cultural and economic factors interact in complex ways and influence caregivers' responses to children with fever. A concise and holistic understanding of context specific caregivers responses and a host of social, economic, cultural conceptual, gender and physical factors that influence those responses is essential to inform the design of appropriate, acceptable and effective behaviour change communication strategies to promote early and effective treatment of malaria fevers in children under the age of five years and living in areas where malaria is endemic.

Efficacy of Arthemether – Lumenfantrine against Uncomplicated Plasmodium falciparum Malaria in Infants and Children in Uyo, Nigeria

Coartem is recently approved artemisininbased tablet that provides effective antimalarial treatment for children in many subsaharan countries. This study evaluates the efficacy of this drug in 120 children weighing 5-25kg with uncomplicated falciparum malaria in Uyo. Six doses of coartem were given over 3 days with follow up at 7, 14 and 28 days. Treatment rapidly cleared parasitaemia and fever. The overall 28-day cure was 80.1%. Cure rate at 7 and 14 days exceeded 90%. No severe adverse side-effects, clinical failures or parasitological failures were observed among these patient. Coartem therefore appear efficacious for the treatment of uncomplicated malaria in Nigeria.

Cost is killing patients: subsidising effective antimalarials

National and global efforts to treat malaria have focused largely on provision of effective antimalarial treatment, mainly through public health services. The private sector (although a key source of antimalarials in most countries) has been mostly ignored in the effort to find solutions to the issues of accessibility, availability, and affordability of effective drugs.1 The cost of artemisinin-based combination treatments (ACTs), the only truly effective antimalarials,2 is far beyond the reach of the average family in Africa, let alone poorer populations.

Malaria treatment: no place like home

If the United Nations Millennium Development Goals are to be met, there is a need to improve access to effective antimalarial treatment where the burden of malaria is highest. Health facilities are often bypassed by communities, and inappropriate and poor-quality self-medication is common. The home management of malaria (HMM) strategy has been shown to have an effect on malaria morbidity and mortality in the chloroquine era, but several evidence gaps remain to be filled to confirm its value in the era of artemisinin-based combination therapies. Nevertheless, if a substantial reduction of the malaria burden is to be achieved, access to effective medicines has to be vastly improved, and in most of sub-Saharan Africa, this will have to be through HMM.

Survival and haematological recovery of children with severe malaria transfused in accordance to WHO guidelines in Kilifi, Kenya

BackgroundSevere anaemia requiring emergency blood transfusion is a common complication of malaria in children. To ensure access for urgent blood transfusion, the World Health Organization has developed clear guidelines with haemoglobin thresholds prevent unwarranted transfusion,. Few studies have reported outcome and haematological recovery of children with severe malaria where transfusion practice complies with WHO recommendations.MethodsA prospective observational study of survivors of severe and complicated malaria transfused in accordance with WHO guidelines. Children were invited for review at one month post-discharge. Non-attendees were traced in the community to ascertain survival.ResultsOutcome was assessed in 213 survivors. Those transfused were younger, had a higher base deficit, mean lactate levels and a higher prevalence of respiratory distress. As expected mean admission haemoglobin (Hb) was significantly lower amongst transfused [5.0 g/dL SD: 1.9] compared to non-transfused children [8.3 g/dL SD: 1.7] (p < 0.001). At discharge mean Hb was similar 6.4 g/dL [SD: 1.5] and 6.8 g/dL [SD: 1.6] respectively (p = 0.08), most children remained moderately to severely anaemic. At one month follow up 166 children (78%) returned, in whom we found no differences in mean Hb between the transfused (10.2 g/dL [SD: 1.7]) and non-transfused (10.0 g/dL [SD: 1.3]) survivors (p = 0.25). The major factors affecting haematological recovery were young age (<24 months) and concomitant malaria parasitaemia; Hb being 8.8 g/dL [SD: 1.5] in parasitaemic individuals compared with 10.5 g/dL [SD: 1.3] in those without (p < 0.001).ConclusionThis data supports the policy of rational use of blood transfusion, as proposed in the WHO guidelines, for children with anaemia in areas where access to emergency transfusion is not guaranteed. We have provided empirical data indicating that transfusion does not influence superior recovery in haemoglobin concentrations and therefore cannot be justified on this basis alone. This may help resolve the disparity between international policy and current clinical practice. Effective anti-malarial treatment at discharge may prevent reoccurrence of anaemia.

The role of anti-malarial drugs in eliminating malaria

Effective anti-malarial drug treatment reduces malaria transmission. This alone can reduce the incidence and prevalence of malaria, although the effects are greater in areas of low transmission where a greater proportion of the infectious reservoir is symptomatic and receives anti-malarial treatment. Effective treatment has greater effects on the transmission of falciparum malaria, where gametocytogenesis is delayed, compared with the other human malarias in which peak gametocytaemia and transmissibility coincides with peak asexual parasite densities. Mature Plasmodium falciparum gametocytes are more drug resistant and affected only by artemisinins and 8-aminoquinolines. The key operational question now is whether primaquine should be added to artemisinin combination treatments for the treatment of falciparum malaria to reduce further the transmissibility of the treated infection. Radical treatment with primaquine plays a key role in the eradication of vivax and ovale malaria. More evidence is needed on the safety of primaquine when administered without screening for G6PD deficiency to inform individual and mass treatment approaches in the context of malaria elimination programmes.

Evolución temporal del hemograma en niños con malaria

Introducción: los estudios colombianos sobre las relaciones entre paludismo, parásitos intestinales, desnutrición y comportamiento del hemograma son muy escasos.Objetivos: conocer los cambios del hemograma en niños de 4 a 10 años de edad, con malaria, seguidos durante 30 días.Metodología: el estudio es parte de un macroproyecto (estudio clínico controlado, grupos paralelos, no ciego).Resultados: se evaluaron 93 niños. Los riesgos de desnutrición fueron: crónica 52%, global 47%, 15% aguda. Se hallaron parásitos intestinales en 88%, que fueron patógenos en 80%; 35% estaban poliparasitados.Hemograma: hemoglobina (promedio): 10,3 g/dL a los días 1 y 8; al día 30: 11,8 g/dL. La desnutrición crónica y la parasitosis intestinal no influyeron significativamente en la hemoglobina en los días 1 y 30. Tuvo más influencia (sin ser estadísticamente significativa) la desnutrición que la parasitosis. Durante el episodio malárico el recuento leucocitario fue normal y pasó en los 30 días siguientes hacia muy leve leucocitosis. El análisis de los leucocitos mostró disminución de los neutrófilos y basófilos, aumento de los eosinófilos, linfocitosis leve y monocitopenia marcada, ambas estables. La linfocitosis y la monocitopenia no coinciden con lo informado por otros autores.Conclusiones: estos niños con malaria (90% por P. vivax), parasitosis intestinal y desnutrición crónica, tuvieron antes del tratamiento anemia homogénea normocítica, de grado leve, que se recuperó en 30 días a partir del tratamiento antimalárico; 80% también tuvieron trombocitopenia; el leucograma mostró, al día 1, neutropenia y basopenia, con eosinofilia, junto con linfocitos normales y monocitopenia marcada. Los niños de nuestras zonas palúdicas están afectados simultáneamente por desnutrición, parasitosis intestinales y malaria. Se requiere tratar al tiempo todas estas enfermedades para mejorar notoriamente el estado de salud.

Communicable diseases in south-east Asia: call for papers

WHO’s South-East Asia Region, comprising 11 member countries, is home to 26% of the world’s population and 30% of the world’s poor.1,2 Of the 14 million deaths that occur annually in this region, 40% are due to communicable diseases compared with the global proportion of 28%.3 A high density of population, poverty, poor sanitation and tropical climate create an environment conducive to the emergence and propagation of communicable diseases.4 As a result, the region is at high risk for new and emerging infectious disease events and has become a hotspot for many zoonoses, drug-resistant pathogens and vector-borne diseases. The region is the epicentre of avian influenza, which has the potential for causing an influenza pandemic. Multidrug-resistant malaria, including artemisinin resistance at the border of Cambodia and Thailand, threatens to jeopardize the provision of effective antimalarial treatment worldwide.5 Chikungunya virus has re-emerged after 30 years, the spread of dengue is expanding geographically, and the impact of climate change on these vector-borne diseases is a matter of increasing concern. As many as 1.3 billion people in the region live in high-risk areas for malaria and dengue fever. The region alone bears 35% of the global burden of tuberculosis, 60% of lymphatic filariasis and 80% of leprosy cases.6 Fortunately, there is a high level of political commitment towards combating both old diseases as well as new and re-emerging ones. Successful examples include eradication of guinea-worm disease, elimination of yaws from India, excellent progress in tuberculosis control and in combating HIV. The opportunities for eliminating diseases such as visceral leishmaniasis are unique to this region. Though polio remains a lingering problem, enormous efforts are being made towards its eradication. Basic systems and human resources are in place and can be used to their full potential. Good work that is already underway needs to be documented and shared more widely. The WHO South-East Asia Region has been undergoing rapid economic development over the past few decades. While this has worked in favour of combating communicable diseases in terms of greater financial resources and priority given to health, it has had profound impact on communicable diseases in the context of globalization. The ease of international travel, population movement, urbanization, unplanned and unregulated developmental activities are all facilitating the spread of diseases, both within and across borders, thus threatening international health security. Furthermore, the economic growth has not been equitable and poor health is both a cause and consequence of non-inclusive growth.7 Innovative strategies are being implemented in the region to address these issues. The social insurance scheme in Thailand,8 national rural health mission in India,9 partnerships between the government and nongovernmental organizations in Bangladesh are just a few example of initiatives that governments are taking to address the concerns of the poor and to ensure equity and social justice in the health area. Core capacity is being built for early detection and rapid response to these new pathogens in the context of the International Health Regulations (IHR 2005). Developing robust health delivery mechanisms is a key area for policy and research. WHO’s South-East Asia Region has a vibrant private health sector, including advanced pharmaceutical and biotechnology research, development and manufacturing capacity, which can be engaged towards further strengthening health services. Existing infrastructure can be used as a foundation to allow appropriate components of communicable disease control to be managed by primary health care. A theme issue of the Bulletin will provide a forum for sharing the region’s successes, and its future opportunities in disease control and research. The issue aims to foster greater international collaboration and partnership. Since the region has such a high communicable disease burden and risk, greater investment and collaboration will benefit not only the communities it serves but the entire world. The deadline for submissions to this issue is 1 June 2009. Manuscripts should be submitted to: http://submit.bwho.org and should respect the Guidelines for Contributors, available at: http://www.who.int/bulletin/volumes/84/current_guidelines/en/index.html. They should be accompanied by a cover letter mentioning this call for papers. All submissions will go through the Bulletin’s peer review process. ■

Malaria in pregnancy in an area of stable and intense transmission: is it asymptomatic?

To report a study of the signs and symptoms of malarial infection during pregnancy in an area of stable and intense transmission. As part of a clinical trial, to assess the efficacy and safety of four antimalarial drug regimens in pregnant women, we collected clinical and laboratory data from 900 parasitaemic pregnant women and 223 non-parasitaemic pregnant women who attended an antenatal clinic at a district hospital in Ghana. Frequencies of signs and symptoms were calculated and their association with the level of parasitaemia was assessed using multivariate logistic regression. History of fever (7.8%vs. 44.4%; P < 0.0001), headache (12.5%vs. 43.9%; P < 0.0001), vomiting (0 vs. 11.5%; P = 0.01), malaise (1.6%vs. 31.6%; P < 0.0001) dizziness (0%vs. 23%; P < 0.0001) and fatigue (0%vs. 22.5%; P < 0.0001) was substantially higher in parasitaemic primigravidae than in aparasitaemic primigravid women. Similar differences in the distribution of the symptoms and signs were observed between parasitaemic and aparasitaemic multigravid women. The proportion of women with elevated concentrations of aspartate aminotransferase, alanine aminotransferase and total bilirubin and its fractions was also higher in parasitaemic than in non-parasitaemic women. In areas of stable malarial transmission, malaria in pregnancy is often symptomatic. Although the symptoms are mostly non-specific, careful recording of history may be useful to identify women who need a confirmatory test and an effective antimalarial treatment.

Hemolytic Anemia and Thromobocytopenia Associated with Ischemic Brain Lesions in Patients with Acute Uncomplicated Plasmodium Falciparum Malaria.

To examine the association between hemolysis in Plasmodium falciparum malaria and brain lesions in the absence of severe or cerebral malaria, we prospectively examined patients at the Bangkok Hospital for Tropical Diseases. We conducted standard physical, neurological and laboratory studies on 10 consecutive adult, non-immune patients admitted with acute uncomplicated falciparum malaria. MR studies of the brain, including T2-weighted and diffusion-weighted sequences, were performed within 24 hours of admission and repeated after 4 weeks using a 3.0 Tesla scanner (Gyroscan Intera Master, Philips). Each patient was fully conscious (Glasgow coma score 14 to 15) and had no abnormality detected on standard neurological evaluation. Within 24 hours, initial MR examinations found a restricted diffusion, ischemic, symmetrical midline lesion in the splenium of the corpus callosum of 4 (40%) of the 10 male patients. On admission, the 4 patients with a splenial lesion had a higher median hematocrit (44 vs. 32%, P<0.04), a higher mean serum indirect bilirubin (2.8 vs. 0.7 mg/dL, P<0.03) and lower mean platelet count (48,500 vs. 129,000 × 1000/microL, P<0.01), as well as a greater fall in hematocrit over the first 3 hospital days (7 vs. 1%, P<0.003) than the remaining 6 patients. No significant differences were found between the 4 patients with and the 6 patients without the splenial lesions with respect to mean age, days of fever before admission, parasite count on admission, parasite count after 24 hours of hospitalization (near the time of the initial MRI examination), and parasite or fever clearance time. After effective antimalarial treatment with artemisinin combination therapy, repeat studies 4 weeks later found resolution of the hematological differences between the groups and no residua of the splenial lesions. We conclude that reversible white matter injury was initially present in at least some nonimmune patients with acute uncomplicated falciparum malaria and resolved after early treatment with potent antimalarial drugs. P. falciparum modifies the surface of infected erythrocytes so that the parasitized red blood cells sequester by adhering to endothelial cells lining the microvasculature of vital organs, especially within the brain. The blood supply to the splenium of the corpus callosum may make this area particularly vulnerable to sequestration of parasitized red blood cells and microvascular obstruction. In addition, platelet-mediated autoagglutination has been reported with falciparum malaria in Thailand. In our patients, increased sequestration and destruction of both red blood cells and platelets in platelet-mediated autoagglutinates may have contributed to the severity of the hemolysis and thrombocytopenia as well as to the microvascular obstruction underlying the lesions in the splenium of the corpus callousum. Episodes of uncomplicated falciparum malaria may be an unrecognized source of neurological disease and disability in affected populations, both in southeast Asia and globally.

Adherence of community caretakers of children to pre-packaged antimalarial medicines (HOMAPAK®) among internally displaced people in Gulu district, Uganda

BackgroundIn 2002, home-based management of fever (HBMF) was introduced in Uganda, to improve access to prompt, effective antimalarial treatment of all fevers in children under 5 years. Implementation is through community drug distributors (CDDs) who distribute pre-packaged chloroquine plus sulfadoxine-pyrimethamine (HOMAPAK®) free of charge to caretakers of febrile children. Adherence of caretakers to this regimen has not been studied.MethodsA questionnaire-based survey combined with inspection of blister packaging was conducted to investigate caretakers' adherence to HOMAPAK®. The population surveyed consisted of internally displaced people (IDPs) from eight camps.ResultsA total of 241 caretakers were interviewed. 95.0% (CI: 93.3% – 98.4%) of their children had received the correct dose for their age and 52.3% of caretakers had retained the blister pack. Assuming correct self-reporting, the overall adherence was 96.3% (CI: 93.9% – 98.7%). The nine caretakers who had not adhered had done so because the child had improved, had vomited, did not like the taste of the tablets, or because they forgot to administer the treatment. For 85.5% of cases treatment had been sought within 24 hours. Blister packaging was considered useful by virtually all respondents, mainly because it kept the drugs clean and dry. Information provided on, and inside, the package was of limited use, because most respondents were illiterate. However, CDDs had often told caretakers how to administer the treatment. For 39.4% of respondents consultation with the CDD was their reported first action when their child has fever and 52.7% stated that they consult her/him if the child does not get better.ConclusionIn IDP camps, the HBMF strategy forms an important component of medical care for young children. In case of febrile illness, most caretakers obtain prompt and adequate antimalarial treatment, and adhere to it. A large proportion of malaria episodes are thus likely to be treated before complications can arise. Implementation in the IDP camps now needs to focus on improving monitoring, supervision and general support to CDDs, as well as on targeting them and caretakers with educational messages. The national treatment policy for uncomplicated malaria has recently been changed to artemether-lumefantrine. Discussions on a suitable replacement combination for HBMF are well advanced, and have raised new questions about adherence.

Population biology and antimalarial resistance: The transmission of antimalarial drug resistance in Plasmodium falciparum

Malaria morbidity and mortality continue to increase across sub-Saharan Africa. This is largely as a result of the continued use of chloroquine and sulfadoxine-pyrimethamine, despite widespread resistance. Although eliminating the asexual stages of Plasmodium falciparum is the focus of treatment of individual symptomatic patients, at a population level, reducing the carriage of gametocytes – the sexual stage responsible for infection of the mosquito vector – is necessary to limit the transmission of malaria parasites and the spread of antimalarial resistance. The probability of a mosquito being infected depends on the prevalence, duration and density of viable gametocyte carriage in the human host, although additional humoral and leukocyte factors also affect transmissibility. There is a log–sigmoid relationship between gametocyte density in the patients’ blood and infectivity to the mosquito. The infectivity and thus transmission potential associated with a particular antimalarial treatment can be characterised as a function of blood gametocyte density and time, summing these over the acute and all subsequent recrudescences of that infection. Gametocyte carriage and infectivity to mosquitoes is consistently higher in patients infected with drug resistant compared with drug sensitive malaria parasites. It is the ratio of transmission potential in drug resistant versus sensitive infections that drives the spread of resistance. Early access to highly effective antimalarial treatment reduces the risk of disease progression and limits gametocyte carriage. The remarkable spread of sulfadoxine-pyrimethamine (SP) resistance across vast regions results from the very high post-treatment prevalence and density of gametocyte carriage following SP treatment. In areas of low intensity malaria transmission, the gametocyte-reducing effect of widespread use of artemisinin-based combination therapy has resulted in a sustained decrease in malaria transmission and a decrease in the spread of resistance. Malaria treatment policy should be based primarily on therapeutic efficacy against asexual stages, but should also consider transmission reduction potential. Artemisinin-based combination therapies are the only antimalarials currently available which rapidly reduce both asexual and gametocyte stages of the P. falciparum lifecycle.

Efficacy and safety of artemether–lumefantrine (Coartem ®) tablets (six-dose regimen) in African infants and children with acute, uncomplicated falciparum malaria

Approximately one million children die from malaria each year. A recently approved artemisinin-based tablet, Coartem (co-artemether), comprising artemether 120 mg plus lumefantrine 20 mg, given in four doses, provides effective antimalarial treatment for children in many sub-Saharan countries. However, this regimen is considered insufficient for non-immune infants and in areas where multidrug-resistant Plasmodium falciparum predominates. This open-label study assessed the efficacy and safety of co-artemether administered to 310 African children weighing 5-25 kg, with acute, uncomplicated falciparum malaria. Six doses of co-artemether were given over 3 days, with follow-up at 7, 14 and 28 days. Treatment rapidly cleared parasitemia and fever. The overall 28-day cure rate was 86.5%, and 93.9% when corrected by PCR for reinfection. Cure rates at 7 and 14 days exceeded 97.0% (uncorrected) and, on day 28, were similar in infants (5-<10 kg) previously exposed to malaria infection (partially immune: 88.6% uncorrected; 93.3% corrected), and in those who were non-immune (82.5% uncorrected; 95.0% corrected). Adverse events were mostly mild. There was no electrocardiographic evidence of cardiotoxicity. The co-artemether six-dose regimen, treating acute uncomplicated falciparum malaria in African children, achieved rapid parasite clearance and a high cure rate. Treatment was generally safe and well tolerated.

Splenic infarction during acute malaria

Malaria is the most frequent cause of fever among travellers returning from tropical countries. Each year about 7000 cases are notified in France, of which 90% are due to Plasmodium falciparum. We describe the case of a Caucasian female patient with no previous exposure to malaria in whom splenic infarction occurred during effective antimalarial treatment for initially uncomplicated acute malaria. Management was restricted to close clinical monitoring and analgesia (subcutaneous morphine). Imaging abnormalities resolved within a few months. We found seven other such cases in the literature. All seven patients were younger and splenic infarction occurred later than in the case we describe. Clinical outcome was favourable in all the cases. It is noteworthy that this rare complication can occur despite appropriate antimalarial prophylaxis and treatment. There are no known predictive signs. Clinicians must be aware that left hypochondrial pain occurring during treatment for acute malaria may be due to splenic infarction.